Human pharmacokinetics of the antiviral drug DHPG

Clin Pharmacol Ther. 1986 Sep;40(3):281-6. doi: 10.1038/clpt.1986.177.

Abstract

The pharmacokinetics of the antiviral drug 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl]guanine (DHPG) were examined in six patients receiving 2.5 or 5.0 mg/kg every 8 or 12 hours for human cytomegalovirus (HCMV) pneumonitis or retinitis. Biexponential decay with a mean distribution t1/2 of 0.23 hours and terminal t1/2 of 2.53 hours was observed. Total clearance correlated well with and exceeded creatinine clearance by a factor of 2.4. Mean volume of the central compartment was 15.26 L/1.73 m2 and the volume of distribution at steady state was 32.8 L/1.73 m2. Peak (model predicted) and trough plasma concentrations were 4.75 to 6.20 micrograms/ml and less than 0.25 to 0.63 microgram/ml, respectively, in patients receiving 2.5 mg/kg. Peak concentrations are well above those needed to inhibit HCMV at the 50% level (ID50) and troughs are near this ID50. Cerebrospinal fluid concentrations of DHPG indicate a penetration of 24% to 67%. No accumulation of DHPG was apparent in these patients. However, dosage reduction is necessary in renal insufficiency. Neutropenia occurred in one patient. The plasma concentration profile of DHPG suggests potential beneficial activity against HCMV.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyclovir / adverse effects
  • Acyclovir / analogs & derivatives*
  • Acyclovir / blood
  • Acyclovir / therapeutic use
  • Adolescent
  • Adult
  • Antiviral Agents / blood*
  • Cytomegalovirus Infections / blood
  • Cytomegalovirus Infections / drug therapy
  • Female
  • Ganciclovir
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Pneumonia / blood
  • Pneumonia / drug therapy
  • Retinitis / blood
  • Retinitis / drug therapy
  • Time Factors

Substances

  • Antiviral Agents
  • Ganciclovir
  • Acyclovir